title: Factors affecting warfarin dose requirements and quality of anticoagulation in adult Egyptian patients: role of gene polymorphism.
abstract: BACKGROUND
  Warfarin is the mainstay of anticoagulation therapy worldwide. CYP2C9 and VKORC1 are two major genetic factors associated with inter-individual and inter-ethnic variability in the warfarin dose.
  
  
  OBJECTIVE
  This study aims to assess the impact of VKORC1-1639G>A polymorphism and the most common CYP2C9 variant alleles (*2 and *3) on warfarin response in Egyptian patients.
  
  
  METHODS
  Genetic analysis of VKORC1-1639G>A and CYP2C9*2, CYP2C9*3 was performed using real-time PCR system. Patients maintained on a constant dose targeting an international normalized ratio range of 2-3.5 for at least three consecutive times were considered as good candidates. A stepwise linear regression analysis was used to determine the independent effects of genetic and non-genetic factors on daily warfarin dose requirements.
  
  
  RESULTS
  Patients carrying VKORC1 and CYP2C9 variant genotypes needed a 44.8 % lower mean daily warfarin dose as compared to wild types. Patients with G allele for VKORC1-1639G>A had a significantly higher number of thromboembolic complications per month during therapy. On the first 30 days of therapy, presence of a variant allele either in VKORC1 or in CYP2C9 was associated with increased time required to achieve stable dosing. Multiple regression analysis showed that, VKORC1-1639G>A, age, CYP2C9*3, and smoking status explained 43.4 % of the overall variability in the warfarin dose.
  
  
  CONCLUSIONS
  VKORC1-1639G>A and CYP2C9 polymorphisms contribute to the difference in warfarin dose requirements and quality of anticoagulation amongst Egyptian patients. Study results support using personalized warfarin treatment in Egyptian patients.
authors.affiliation: Critical Care Medicine Department, Cairo University Hospitals, Cairo, Egypt, naglaabazan@yahoo.com.
authors.forename: N S
authors.initials: NS
authors.lastname: Bazan
authors.forename: N A
authors.initials: NA
authors.lastname: Sabry
authors.forename: A
authors.initials: A
authors.lastname: Rizk
authors.forename: S
authors.initials: S
authors.lastname: Mokhtar
authors.forename: O A
authors.initials: OA
authors.lastname: Badary
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000483:Alleles; D000925:Anticoagulants / Q000008:administration & dosage*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065729:Cytochrome P-450 CYP2C9; D004534:Egypt; D005260:Female; D005838:Genotype; D006801:Humans; D019934:International Normalized Ratio; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000502:physiology*; D057285:Precision Medicine; D012044:Regression Analysis; D012907:Smoking; D013923:Thromboembolism / Q000235:genetics*; D064417:Vitamin K Epoxide Reductases / Q000235:genetics*; D014859:Warfarin / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D014859:Warfarin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases